Effects of cAMP, glucocorticoids, and calcium on dopamine beta-hydroxylase gene expression in bovine chromaffin cells.

Abstract

To better understand the molecular mechanism underlying regulation of bovine dopamine beta-hydroxylase (DBH), the effects of elevated intracellular cAMP, glucocorticoids, and calcium were studied in primary cultured chromaffin cells. Elevation of intracellular cAMP by forskolin and treatment with its analog 8-bromo-cAMP caused an increase in the bovine DBH mRNA level by 3.5 +/- 0.5- and 7.8 +/- 0.9-fold, respectively, which was maximal at 6 h after the treatments. On the other hand, dexamethasone elicited no apparent change in DBH gene expression at various concentrations and time. The combined treatment with forskolin and dexamethasone resulted in the same degree of increase as that with forskolin alone. Increased intracellular calcium by the ionophore A23187 ranging from 50 to 500 nM caused DBH mRNA to decrease, which began to be observed after 6 h and was undetectable by 48 h. The results demonstrate the existence of coordinate and differential regulations among the enzymes involved in catecholamine biosynthesis in bovine adrenomedullary cells.